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Disturbances in Muscle Energy Metabolism in Patients with Amyotrophic Lateral Sclerosis. | LitMetric

AI Article Synopsis

  • - ALS is a severe neuromuscular disease that leads to muscle wasting and spasticity, primarily causing death by respiratory failure due to the degeneration of motor neurons.
  • - A study analyzed blood plasma from 25 ALS patients and 25 control subjects, revealing decreased total protein levels, unchanged essential amino acids, but increased glutamine levels and reduced creatinine, which suggests metabolic changes in energy utilization and muscle catabolism in ALS patients.
  • - The research utilized a Random Forest algorithm for data analysis, achieving high accuracy in distinguishing ALS patients from control subjects based on plasma metabolite levels, indicating potential for using these metabolites as biomarkers in ALS diagnosis.

Article Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal neuromuscular disease type of motor neuron disorder characterized by degeneration of the upper and lower motor neurons resulting in dysfunction of the somatic muscles of the body. The ALS condition is manifested in progressive skeletal muscle atrophy and spasticity. It leads to death, mostly due to respiratory failure. Within the pathophysiology of the disease, muscle energy metabolism seems to be an important part. In our study, we used blood plasma from 25 patients with ALS diagnosed by definitive El Escorial criteria according to ALSFR-R (Revised Amyotrophic Lateral Sclerosis Functional Rating Scale) criteria and 25 age and sex-matched subjects. Aside from standard clinical biochemical parameters, we used the NMR (nuclear magnetic resonance) metabolomics approach to determine relative plasma levels of metabolites. We observed a decrease in total protein level in blood; however, despite accelerated skeletal muscle catabolism characteristic for ALS patients, we did not detect changes in plasma levels of essential amino acids. When focused on alterations in energy metabolism within muscle, compromised creatine uptake was accompanied by decreased plasma creatinine. We did not observe changes in plasma levels of BCAAs (branched chain amino acids; leucine, isoleucine, valine); however, the observed decrease in plasma levels of all three BCKAs (branched chain alpha-keto acids derived from BCAAs) suggests enhanced utilization of BCKAs as energy substrate. Glutamine, found to be increased in blood plasma in ALS patients, besides serving for ammonia detoxification, could also be considered a potential TCA (tricarboxylic acid) cycle contributor in times of decreased pyruvate utilization. When analyzing the data by using a cross-validated Random Forest algorithm, it finished with an AUC of 0.92, oob error of 8%, and an MCC (Matthew's correlation coefficient) of 0.84 when relative plasma levels of metabolites were used as input variables. Although the discriminatory power of the system used was promising, additional features are needed to create a robust discriminatory model.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11278632PMC
http://dx.doi.org/10.3390/metabo14070356DOI Listing

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